The major aim of this research is to gain an understanding of the mechanisms which at the cellular and molecular level control the growth of the isolated adult cardiac myocyte. This research will be undertaken in tissue culture utilizing carefully defined conditions (i.e. serum-free media) and recent advances in molecular biology (In situ hybridization and S1 nuclease protection experiments with Alpha and Beta specific probes, monoclonal antibodies to Alpha and Beta isomyosins) to examine the effects of neural and neurohumoral influences on myocyte differentiation. We will examine the synthesis of contractile proteins, in particular myosin and the regulation of this synthesis at the molecular level. Additionally, the relationship between neural and neurohumoral influences and myocyte proliferation will be studied. The use of tissue culture will permit the analysis of specific variables as opposed to the complicated systemic interactions which usually affect the interpretation of in vivo experiments. The successful completion of this proposed research will permit a clearer insight into those factors controlling cardiac myocyte growth and adaptation to stress.